Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11.

Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD1-5. This non-canonical inflammasome defends against Gram-negative bacteria6,7. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis8. S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD+ donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADP-riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11- and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis.

Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7.

Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.

Legionella effectors SidC/SdcA ubiquitinate multiple small GTPases and SNARE proteins to promote phagosomal maturation.

Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs.

The Salmonella Typhimurium Effector SpvB Subverts Host Membrane Trafficking by Targeting Clathrin and AP-1.

Salmonella enterica, the etiological agent of gastrointestinal and systemic diseases, translocates a plethora of virulence factors through its type III secretion systems to host cells during infection. Among them, SpvB has been reported to harbor an ADP-ribosyltransferase domain in its C terminus, which destabilizes host cytoskeleton by modifying actin. However, whether this effector targets other host factors as well as the function of its N terminus still remains to be determined. Here, we found that SpvB targets clathrin and its adaptor AP-1 (adaptor protein 1) via interactions with its N-terminal domain. Notably, our data suggest that SpvB-clathrin/AP-1 associations disrupt clathrin-mediated endocytosis and protein secretion pathway as well. In addition, knocking down of AP-1 promotes Salmonella intracellular survival and proliferation in host cells.

Coxiella burnetii inhibits host immunity by a protein phosphatase adapted from glycolysis.

Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella-containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii, CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.

Analysis of the Long Non-Coding and Messenger RNA Expression Profiles in the Skin Tissue of Super Merino and Small-Tailed Han Sheep.

Wool quality and yield are two important economic livestock traits. However, there are relatively few molecular studies on lncRNA for improving sheep wool, so these require further exploration. In this study, we examined skin tissue from the upper scapula of Super Merino (SM) and Small-Tailed Han (STH) sheep during the growing period. The apparent difference was verified via histological examination. High-throughput RNA sequencing identified differentially expressed (DE) long non-coding (lncRNAs) and messenger RNAs (mRNAs). The target gene of DE lncRNA and DE genes were enrichment analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify randomly selected DE lncRNAs and mRNAs. Finally, the DE, RAC2, WNT11, and FZD2 genes, which were enriched in the Wnt signaling pathway, were detected via immunohistochemistry. The results showed that a total of 20,888 lncRNAs and 31,579 mRNAs were identified in the skin tissues of the two sheep species. Among these, 56 lncRNAs and 616 mRNAs were differentially expressed. Through qRT-PCR, the trends in the randomly selected DE genes' expression were confirmed to be aligned with the RNA-seq results. GO and KEGG enrichment analysis showed that DE lncRNA target genes were enriched in GO terms as represented by epidermal and skin development and keratin filature and in KEGG terms as represented by PI3K-Akt, Ras, MAPK, and Wnt signaling pathways, which were related to hair follicle growth and development. Finally, immunohistochemistry staining results indicated that RAC2, WNT11, and FZD2 were expressed in dermal papilla (DP). The lncRNAs MSTRG.9225.1 and MSTRG.98769.1 may indirectly participate in the regulation of hair follicle growth, development, and fiber traits by regulating their respective target genes, LOC114113396(KRTAP15-1), FGF1, and IGF1. In addition, MSTRG.84658.1 may regulate the Wnt signaling pathway involved in the development of sheep hair follicles by targeting RAC2. This study provides a theoretical reference for improving sheep breeding in the future and lays a foundation for further research on the effects of MSTRG.84658.1 and the target gene RAC2 on dermal papilla cells (DPC).

The ever-increasing necessity of mass spectrometry in dissecting protein post-translational modifications catalyzed by bacterial effectors.

Protein post-translational modifications (PTMs), such as ADP-ribosylation and phosphorylation, regulate multiple fundamental biological processes in cells. During bacterial infection, effector proteins are delivered into host cells through dedicated bacterial secretion systems and can modulate important cellular pathways by covalently modifying their host targets. These strategies enable intruding bacteria to subvert various host processes, thereby promoting their own survival and proliferation. Despite rapid expansion of our understanding of effector-mediated PTMs in host cells, analytical measurements of these molecular events still pose significant challenges in the study of host-pathogen interactions. Nevertheless, with major technical breakthroughs in the last two decades, mass spectrometry (MS) has evolved to be a valuable tool for detecting protein PTMs and mapping modification sites. Additionally, large-scale PTM profiling, facilitated by different enrichment strategies prior to MS analysis, allows high-throughput screening of host enzymatic substrates of bacterial effectors. In this review, we summarize the advances in the studies of two representative PTMs (i.e., ADP-ribosylation and phosphorylation) catalyzed by bacterial effectors during infection. Importantly, we will discuss the ever-increasing role of MS in understanding these molecular events and how the latest MS-based tools can aid in future studies of this booming area of pathogenic bacteria-host interactions.

Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination.

The Legionella pneumophila effector MavC induces ubiquitination of the E2 ubiquitin-conjugating enzyme UBE2N by transglutamination, thereby abolishing its function in the synthesis of K63 -type polyubiquitin chains. The inhibition of UBE2N activity creates a conundrum because this E2 enzyme is important in multiple signaling pathways, including some that are important for intracellular L. pneumophila replication. Here, we show that prolonged inhibition of UBE2N activity by MavC restricts intracellular bacterial replication and that the activity of UBE2N is restored by MvcA, an ortholog of MavC (50% identity) with ubiquitin deamidase activity. MvcA functions to deubiquitinate UBE2N-Ub using the same catalytic triad required for its deamidase activity. Structural analysis of the MvcA-UBE2N-Ub complex reveals a crucial role of the insertion domain in MvcA in substrate recognition. Our study establishes a deubiquitination mechanism catalyzed by a deamidase, which, together with MavC, imposes temporal regulation of the activity of UBE2N during L. pneumophila infection.

Simultaneous measurement of bidirectional magnetic field and temperature with a dual-channel sensor based on the whispering gallery mode.

What we believe is a novel dual-channel whispering gallery mode (WGM) sensor for concurrently measuring bidirectional magnetic field and temperature is proposed and demonstrated. Two sensing microcavities [magnetic fluid (MF)-infiltrated capillary and polydimethylsiloxane (PDMS)-coated microbottle, respectively, referred as Channel 1 (CH1) and Channel 2 (CH2)] are integrated into a silica capillary to facilitate the dual-channel design. Resonant wavelengths corresponding to CH1 and CH2 mainly depend on the change in the magneto-induced refractive index and the change in the thermo-induced parameter (volume and refractive index) of the employed functional materials, respectively. The MF-infiltrated capillary enables bidirectional magnetic field sensing with maximum sensitivities of 46 pm/mT and -3 pm/mT, respectively. The PDMS-coated structure can realize the temperature measurement with a maximum sensitivity of 79.7 pm/°C. The current work possesses the advantage of bidirectionally magnetic tunability besides the temperature response, which is expected to be used in field such as vector magnetic fields and temperature dual-parameter sensing.

Enhanced sensitivity of temperature and magnetic field sensor based on FPIs with Vernier effect.

A kind of temperature and magnetic field sensor using Fabry-Perot interferometers (FPIs) and Vernier effect to enhance sensitivity is proposed. The sensor structure involves filling the FP air cavities with polydimethylsiloxane (PDMS) and magnetic fluid (MF) to create the PDMS and MF cavities for temperature and magnetic field detection, respectively. The two cavities are reflective structures, which are interconnected in series through a fiber-optic circulator. Experimental data demonstrates that the Vernier effect effectively enhances the sensor sensitivity. The average temperature sensitivity of the sensor is 26765 pm/°C within the range of 35∼39.5°C. The magnetic field intensity sensitivity is obtained to be -2245 pm/mT within the range of 3∼11 mT. The sensitivities of the temperature and magnetic field using the Vernier effect are about five times larger than those of the corresponding single FP cavity counterparts.

High-sensitivity vector magnetic field sensor based on a V-shaped multimode-no-core-multimode fiber structure.

This work proposes and investigates a bent multimode-no-core-multimode optical fiber structure for vector magnetic field sensing applications. The bent no-core fiber (NCF) serves as the sensing area, and the gold film is deposited on its surface to excite the surface plasmon resonance effect. Due to the strong evanescent field of the unclad and bent NCF, the as-fabricated sensor exhibits a high sensitivity of 5630 nm/RIU in the refractive index range of 1.36-1.39. Magnetic fluid is employed as the magneto-sensitive material for magnetic field sensing, exhibiting a high magnetic field intensity sensitivity of 5.74 nm/mT and a high magnetic field direction sensitivity of 0.22 nm/°. The proposed sensor features a simple structure, low cost, point sensing, and excellent mechanical performance.

The toxicity response of the electrochemical signal of the cell to the drug metabolized by the S9 system.

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.

Reporting of Ethical Considerations in Qualitative Research Utilizing Social Media Data on Public Health Care: Scoping Review.

BACKGROUND: The internet community has become a significant source for researchers to conduct qualitative studies analyzing users' views, attitudes, and experiences about public health. However, few studies have assessed the ethical issues in qualitative research using social media data. OBJECTIVE: This study aims to review the reportage of ethical considerations in qualitative research utilizing social media data on public health care. METHODS: We performed a scoping review of studies mining text from internet communities and published in peer-reviewed journals from 2010 to May 31, 2023. These studies, limited to the English language, were retrieved to evaluate the rates of reporting ethical approval, informed consent, and privacy issues. We searched 5 databases, that is, PubMed, Web of Science, CINAHL, Cochrane, and Embase. Gray literature was supplemented from Google Scholar and OpenGrey websites. Studies using qualitative methods mining text from the internet community focusing on health care topics were deemed eligible. Data extraction was performed using a standardized data extraction spreadsheet. Findings were reported using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. RESULTS: After 4674 titles, abstracts, and full texts were screened, 108 studies on mining text from the internet community were included. Nearly half of the studies were published in the United States, with more studies from 2019 to 2022. Only 59.3% (64/108) of the studies sought ethical approval, 45.3% (49/108) mentioned informed consent, and only 12.9% (14/108) of the studies explicitly obtained informed consent. Approximately 86% (12/14) of the studies that reported informed consent obtained digital informed consent from participants/administrators, while 14% (2/14) did not describe the method used to obtain informed consent. Notably, 70.3% (76/108) of the studies contained users' written content or posts: 68% (52/76) contained verbatim quotes, while 32% (24/76) paraphrased the quotes to prevent traceability. However, 16% (4/24) of the studies that paraphrased the quotes did not report the paraphrasing methods. Moreover, 18.5% (20/108) of the studies used aggregated data analysis to protect users' privacy. Furthermore, the rates of reporting ethical approval were different between different countries (P=.02) and between papers that contained users' written content (both direct and paraphrased quotes) and papers that did not contain users' written content (P<.001). CONCLUSIONS: Our scoping review demonstrates that the reporting of ethical considerations is widely neglected in qualitative research studies using social media data; such studies should be more cautious in citing user quotes to maintain user privacy. Further, our review reveals the need for detailed information on the precautions of obtaining informed consent and paraphrasing to reduce the potential bias. A national consensus of ethical considerations such as ethical approval, informed consent, and privacy issues is needed for qualitative research of health care using social media data of internet communities.

Pre-treatment assessment of chemotherapy for cancer patients: a multi-site evidence implementation project of 74 hospitals in China.

BACKGROUND: Chemotherapy, whilst treating tumours, can also lead to numerous adverse reactions such as nausea and vomiting, fatigue and kidney toxicity, threatening the physical and mental health of patients. Simultaneously, misuse of chemotherapeutic drugs can seriously endanger patients' lives. Therefore, to maintain the safety of chemotherapy for cancer patients and to reduce the incidence of adverse reactions to chemotherapy, many guidelines state that a comprehensive assessment of the cancer patient should be conducted and documented before chemotherapy. This recommended procedure, however, has yet to be extensively embraced in Chinese hospitals. As such, this study aimed to standardise the content of pre-chemotherapy assessment for cancer patients in hospitals and to improve nurses' adherence to pre-chemotherapy assessment of cancer patients by conducting a national multi-site evidence implementation in China, hence protecting the safety of cancer patients undergoing chemotherapy and reducing the incidence of adverse reactions to chemotherapy in patients. METHODS: The national multi-site evidence implementation project was launched by a JBI Centre of Excellence in China and conducted using the JBI approach to evidence implementation. A pre- and post-audit approach was used to evaluate the effectiveness of the project. This project had seven phases: training, planning, baseline audit, evidence implementation, two rounds of follow-up audits (3 and 9 months after evidence implementation, respectively) and sustainability assessment. A live online broadcast allowed all participating hospitals to come together to provide a summary and feedback on the implementation of the project. RESULTS: Seventy-four hospitals from 32 cities in China participated in the project, four withdrew during the project's implementation, and 70 hospitals completed the project. The pre-and post-audit showed a significant improvement in the compliance rate of nurses performing pre-chemotherapy assessments for cancer patients. Patient satisfaction and chemotherapy safety were also improved through the project's implementation, and the participating nurses' enthusiasm and belief in implementing evidence into practice was increased. CONCLUSION: The study demonstrated the feasibility of academic centres working with hospitals to promote the dissemination of evidence in clinical practice to accelerate knowledge translation. Further research is needed on the effectiveness of cross-regional and cross-organisational collaborations to facilitate evidence dissemination.

Bartonella type IV secretion effector BepC induces stress fiber formation through activation of GEF-H1.

Bartonella T4SS effector BepC was reported to mediate internalization of big Bartonella aggregates into host cells by modulating F-actin polymerization. After that, BepC was indicated to induce host cell fragmentation, an interesting cell phenotype that is characterized by failure of rear-end retraction during cell migration, and subsequent dragging and fragmentation of cells. Here, we found that expression of BepC resulted in significant stress fiber formation and contractile cell morphology, which depended on combination of the N-terminus FIC (filamentation induced by c-AMP) domain and C-terminus BID (Bartonella intracellular delivery) domain of BepC. The FIC domain played a key role in BepC-induced stress fiber formation and cell fragmentation because deletion of FIC signature motif or mutation of two conserved amino acid residues abolished BepC-induced cell fragmentation. Immunoprecipitation confirmed the interaction of BepC with GEF-H1 (a microtubule-associated RhoA guanosine exchange factor), and siRNA-mediated depletion of GEF-H1 prevented BepC-induced stress fiber formation. Interaction with BepC caused the dissociation of GEF-H1 from microtubules and activation of RhoA to induce formation of stress fibers. The ROCK (Rho-associated protein kinase) inhibitor Y27632 completely blocked BepC effects on stress fiber formation and cell contractility. Moreover, stress fiber formation by BepC increased the stability of focal adhesions, which consequently impeded rear-edge detachment. Overall, our study revealed that BepC-induced stress fiber formation was achieved through the GEF-H1/RhoA/ROCK pathway.

In-line temperature-compensated vector magnetic field sensor with side-polished fiber.

A novel, to the best of our knowledge, vector magnetic field sensor with temperature compensation is proposed and investigated. The proposed sensor is realized by side polishing a multi-mode optical fiber and adopting the surface plasmon resonance (SPR) effect. The side-polished surface is coated with a magnetic fluid (MF) and polydimethylsiloxane (PDMS) successively along the fiber axis. The as-fabricated sensor can be used not only for magnetic field strength and direction sensing, but also for temperature detection. The achieved magnetic field intensity sensitivities are 1720 pm/mT (90° direction) and -710 pm/mT (0° direction), and the temperature sensitivity is -2070 pm/°C. On top of its temperature compensation ability, the easy fabrication and very high sensitivity of the proposed sensor are attractive features for vector magnetic field sensing applications.

HIV testing and related factors among 50 years and older MSM in China: results from a cross-sectional study.

ABSTRACTHIV prevalence has increased continuously, and the age groups most afflicted by the epidemic have also shifted to people aged above 50 years. Informed by the theory of HBM, we aimed to investigate related factors associated with regular HIV testing behavior. Cross-sectional data were collected using online questionnaire from geosocial networking (GSN) mobile application (apps) for MSM during May 2020 (N = 1259). Data were analyzed by univariate and multivariate logistic regression. Around 62.0% (n = 781) had received HIV testing before. Participants being divorced/widowed (AOR = 1.5,95%CI:1.1-2.0), being aware of HIV/AIDS-related knowledge (AOR = 1.8,95%CI:1.4-2.3), having disclosed sexual orientation (AOR = 1.9,95%CI:1.5-2.5), ever had sexually transmitted infections symptoms (STIs)before (AOR = 2.4,95%CI:1.8-3.2), having had≥2 sexual partners (AOR = 1.8,95%CI:1.4-2.3) and with high self-efficacy (AOR = 1.1,95%CI:1.0-1.1) were more likely to receive HIV testing. Findings suggest that many Chinses MSM aged 50 and above have not been tested for HIV. Interventions for promoting HIV testing should focus on expanding scales of HIV/STIs screening, providing HIV/AIDS-related knowledge, creating a more supportive social environment and improving self-efficacy of HIV testing.

Single atom alloy clusters Agn-1X- (X = Cu, Au; n = 7-20) reacting with O2: Symmetry-adapted orbital model.

Single atom alloy AgCu catalysts have attracted great attention, since doping the single Cu atom introduces narrow free-atom-like Cu 3d states in the electronic structure. These peculiar electronic states can reduce the activation energies in some reactions and offer valuable guidelines for improving catalytic performance. However, the geometric tuning effect of single Cu atoms in Ag catalysts and the structure-activity relationship of AgCu catalysts remain unclear. Here, we prepared well-resolved pristine Agn - as well as single atom alloy Agn-1Cu- and Agn-1Au- (n = 7-20) clusters and investigated their reactivity with O2. We found that replacing an Ag atom in Agn - (n = 15-18) with a Cu atom significantly increases the reactivity with O2, while replacement of an Ag with an Au atom has negligible effects. The adsorption of O2 on Agn - or Agn-1Cu- clusters follows the single electron transfer mechanism, in which the cluster activity is dependent on two descriptors, the energy level of α-HOMO (strong correlation) and the α-HOMO-LUMO gap (weak correlation). Our calculation demonstrated that the cluster arrangements caused by single Cu atom alloying would affect the above activity descriptors and, therefore, regulates clusters' chemical activity. In addition, the observed reactivity of clusters in the representative sizes with n = 17-19 can also be interpreted using the symmetry-adapted orbital model. Our work provides meaningful information to understand the chemical activities of related single-atom-alloy catalysts.

HIV-related stigma, depression and suicidal ideation among HIV-positive MSM in China: a moderated mediation model.

BACKGROUND: As the HIV epidemic among MSM in China continues, Chinese men who have sex with men (MSM) face various mental health difficulties, including suicide ideation, depression, and stigma. The current study aims to assess the mechanisms between HIV-related stigma, depression, and suicidal ideation among MSM in China. METHODS: This national cross-sectional study was completed on the geosocial networking application (GSN) app, Blued, from December 2020 to March 2021. We used the HIV Stigma Scale and the Center for Epidemiologic Studies Depression Scale (CES-D10) to measure HIV stigma and depression, respectively. Suicidal ideation was measured by the suicidal ideation-related item. Descriptive analyses, logistic regression, and structural equation modeling (SEM) were used for data analysis. RESULTS: A total of 244 HIV-positive MSM were included in the analysis. The mediation model revealed that the direct pathway of perceived HIV-related stigma on suicidal ideation was significant (standardized pathway coefficient = 0.07), and the indirect pathway of perceived HIV-related stigma on suicidal ideation via depression was also significant (standardized pathway coefficient = 0.04). There was a partial mediating effect of depression in the association between perceived HIV-related stigma and suicidal ideation. CONCLUSIONS: Our study found that both perceived HIV-related stigma and depression were associated with suicidal ideation among HIV-positive MSM in China, and that depression could serve as a mediator between HIV-related stigma and suicidal ideation. Targeted interventions regarding HIV-related stigma and depression should be taken into account to reduce suicidal ideation among HIV-positive MSM in China.

Integrative metabolomics and network pharmacology to study the preventative impact of dioscin treatment on hyperuricemia.

This work aims to combine network pharmacology and metabolomics to explore the mechanism of action of dioscin on hyperuricemia (HUA). The preventative impact of dioscin on HUA and its putative mechanism were examined using network pharmacological analysis and metabonomics. Network pharmacology study further pointed out the potential targets of dioscin after a review of the relevant biomarker pathways discovered by metabolomic analysis. Molecular docking was then used to examine how the active chemicals interacted with the target proteins. The therapeutic effect of dioscin on HUA was shown to be mediated by 13 potentially important metabolites as a result of metabonomic research. Most of these metabolites are regulated after dioscin therapy to help patients recover. Based on network pharmacology, we identified 10 central genes, which is partly in agreement with metabolomics data. Using metabolomics and network pharmacology, this study investigated the primary targets and mechanisms of dioscin in the treatment of HUA. It is advantageous that dioscin has been developed as an additional drug for the treatment of HUA.